Mutagenetix > Incidental Mutation

Incidental Mutation 'R4035:Hcn4'

313676

Institutional Source

Beutler Lab

Gene Symbol

Hcn4

Ensembl Gene

ENSMUSG00000032338

Gene Name

hyperpolarization-activated, cyclic nucleotide-gated K+ 4

Synonyms

MMRRC Submission

041613-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4035 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

58823412-58863175 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 58843889 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 266 (D266G)

Ref Sequence

ENSEMBL: ENSMUSP00000034889 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000034889]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000034889
AA Change: D266G

PolyPhen 2 Score 0.387 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000034889
Gene: ENSMUSG00000032338
AA Change: D266G

Domain	Start	End	E-Value	Type
low complexity region	27	39	N/A	INTRINSIC
low complexity region	43	59	N/A	INTRINSIC
low complexity region	97	120	N/A	INTRINSIC
low complexity region	150	184	N/A	INTRINSIC
Pfam:Ion_trans_N	218	261	1.2e-23	PFAM
Pfam:Ion_trans	262	525	2.2e-25	PFAM
low complexity region	526	537	N/A	INTRINSIC
Blast:cNMP	538	570	9e-13	BLAST
cNMP	595	708	2.27e-23	SMART
low complexity region	761	771	N/A	INTRINSIC
low complexity region	775	796	N/A	INTRINSIC
low complexity region	808	818	N/A	INTRINSIC
low complexity region	831	856	N/A	INTRINSIC
low complexity region	866	906	N/A	INTRINSIC
low complexity region	915	930	N/A	INTRINSIC
low complexity region	931	956	N/A	INTRINSIC
low complexity region	960	987	N/A	INTRINSIC
low complexity region	991	1004	N/A	INTRINSIC
low complexity region	1021	1036	N/A	INTRINSIC
low complexity region	1045	1073	N/A	INTRINSIC
low complexity region	1123	1140	N/A	INTRINSIC
low complexity region	1154	1164	N/A	INTRINSIC

Meta Mutation Damage Score

0.9556

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 97.1%
20x: 94.5%

Validation Efficiency

100% (51/51)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the hyperpolarization-activated cyclic nucleotide-gated potassium channels. The encoded protein shows slow kinetics of activation and inactivation, and is necessary for the cardiac pacemaking process. This channel may also mediate responses to sour stimuli. Mutations in this gene have been linked to sick sinus syndrome 2, also known as atrial fibrillation with bradyarrhythmia or familial sinus bradycardia. Two pseudogenes have been identified on chromosome 15. [provided by RefSeq, Oct 2008]
PHENOTYPE: Mice homozygous for disruptions in this gene experience embryonic lethality between E9.5 and E11.5. Conditional deletion in cardiac tissue results in severe bradycardia and death. Mice over-expressing the gene exhibit impaired firing rate in ORN, small olfactory bulb and reduced glomeruli. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 52 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700013D24Rik	A	G	6: 124,356,920	F34L	probably benign	Het
Abcb8	A	G	5: 24,400,621	S168G	probably benign	Het
Ano5	A	G	7: 51,566,485		probably benign	Het
Api5	C	T	2: 94,425,613	R243Q	possibly damaging	Het
Bhlhe41	A	G	6: 145,863,028	S353P	probably benign	Het
Ccdc88c	G	A	12: 100,930,524	A1389V	possibly damaging	Het
Cep350	T	C	1: 155,959,795	T52A	probably benign	Het
Coro2b	A	G	9: 62,425,789		probably benign	Het
Ctcf	A	T	8: 105,664,157	E132V	possibly damaging	Het
Cwf19l2	A	T	9: 3,456,803	H712L	probably benign	Het
Cxcl2	A	T	5: 90,904,413	Q87L	possibly damaging	Het
D3Ertd254e	T	G	3: 36,164,840	H337Q	possibly damaging	Het
Dopey1	T	C	9: 86,494,433	V240A	probably damaging	Het
Etfdh	C	T	3: 79,613,711	V294I	probably benign	Het
Fnip2	C	T	3: 79,479,501	V973I	probably benign	Het
Fyco1	T	C	9: 123,801,283	T1286A	probably benign	Het
Gbp10	T	A	5: 105,224,458	E145D	possibly damaging	Het
Gm13084	T	A	4: 143,810,456	D435V	probably benign	Het
Gsdme	A	T	6: 50,229,448	N138K	possibly damaging	Het
Henmt1	T	C	3: 108,958,685	V199A	probably damaging	Het
Hmcn2	A	T	2: 31,336,612	K200*	probably null	Het
Hmgcr	C	G	13: 96,651,063	L852F	probably damaging	Het
Ifi203	T	A	1: 173,929,474		probably benign	Het
Isl2	A	G	9: 55,542,470	S119G	probably benign	Het
Krba1	A	G	6: 48,411,680	N538D	probably damaging	Het
Lcorl	A	T	5: 45,734,041	N323K	possibly damaging	Het
Mfsd2b	A	G	12: 4,870,578	S80P	probably damaging	Het
Ndst4	C	T	3: 125,438,736	T318M	probably damaging	Het
Nlrp4f	T	C	13: 65,194,007	N608S	probably benign	Het
Nolc1	GCA	GCACCA	19: 46,081,358		probably benign	Het
Olfr212	A	G	6: 116,516,629	N284S	possibly damaging	Het
Olfr878	G	A	9: 37,918,641		probably benign	Het
Osbpl2	G	A	2: 180,161,560	R475H	probably damaging	Het
Ppfibp1	A	G	6: 146,996,836	K97E	probably damaging	Het
Prpsap1	A	T	11: 116,473,008	M263K	probably benign	Het
Prtg	G	T	9: 72,842,709	E132*	probably null	Het
Ptch1	T	G	13: 63,524,959	E944A	probably benign	Het
Rttn	T	C	18: 88,995,653	V482A	probably benign	Het
Samsn1	A	G	16: 75,909,185	M1T	probably null	Het
Scel	A	G	14: 103,530,004	N33S	probably damaging	Het
Sema4g	A	T	19: 45,001,414	Y644F	probably damaging	Het
Slc39a10	G	A	1: 46,812,074	T752M	probably damaging	Het
Snx27	T	C	3: 94,524,244	D281G	probably damaging	Het
Spesp1	T	A	9: 62,273,036	I197L	probably benign	Het
Srsf4	C	T	4: 131,900,102		probably benign	Het
Tpgs1	A	G	10: 79,669,365		probably null	Het
Trpc2	G	A	7: 102,084,504	S220N	probably damaging	Het
Ttk	C	A	9: 83,854,837	P450T	possibly damaging	Het
Ttn	T	G	2: 76,909,821	Q3458P	probably benign	Het
Ube2z	A	G	11: 96,061,067	F152L	probably damaging	Het
Utp20	C	T	10: 88,762,806	V103I	probably benign	Het
Zfa-ps	T	A	10: 52,544,540		noncoding transcript	Het

Other mutations in Hcn4

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00486:Hcn4	APN	9	58860053	missense	unknown
IGL00939:Hcn4	APN	9	58843927	missense	probably benign	0.39
IGL01154:Hcn4	APN	9	58859079	missense	unknown
IGL01408:Hcn4	APN	9	58859886	missense	unknown
IGL02658:Hcn4	APN	9	58859465	missense	unknown
IGL02877:Hcn4	APN	9	58859167	missense	unknown
IGL03211:Hcn4	APN	9	58858151	missense	unknown
PIT1430001:Hcn4	UTSW	9	58859550	missense	unknown
R0049:Hcn4	UTSW	9	58860299	missense	probably damaging	0.98
R0268:Hcn4	UTSW	9	58860162	missense	unknown
R0812:Hcn4	UTSW	9	58823512	start codon destroyed	probably null
R2121:Hcn4	UTSW	9	58824058	missense	unknown
R3035:Hcn4	UTSW	9	58823680	missense	unknown
R3715:Hcn4	UTSW	9	58844036	missense	unknown
R3737:Hcn4	UTSW	9	58843889	missense	probably benign	0.39
R3958:Hcn4	UTSW	9	58844048	missense	unknown
R4393:Hcn4	UTSW	9	58844300	missense	unknown
R4418:Hcn4	UTSW	9	58843895	missense	probably benign	0.39
R4532:Hcn4	UTSW	9	58857798	missense	unknown
R4765:Hcn4	UTSW	9	58857977	missense	unknown
R4857:Hcn4	UTSW	9	58859570	missense	unknown
R4967:Hcn4	UTSW	9	58859828	missense	unknown
R5068:Hcn4	UTSW	9	58860021	missense	unknown
R5253:Hcn4	UTSW	9	58824275	missense	unknown
R5304:Hcn4	UTSW	9	58843932	missense	probably benign	0.39
R5600:Hcn4	UTSW	9	58859293	splice site	probably null
R6346:Hcn4	UTSW	9	58859044	missense	unknown
R6575:Hcn4	UTSW	9	58824152	missense	unknown
R6622:Hcn4	UTSW	9	58857727	missense	unknown
R6967:Hcn4	UTSW	9	58823945	missense	unknown
R7038:Hcn4	UTSW	9	58823584	missense	unknown
R7054:Hcn4	UTSW	9	58855717	missense	unknown
R7229:Hcn4	UTSW	9	58853399	missense	unknown
R7407:Hcn4	UTSW	9	58859370	missense	unknown
R7448:Hcn4	UTSW	9	58844299	missense	unknown
R7531:Hcn4	UTSW	9	58860137	missense	unknown
R7572:Hcn4	UTSW	9	58823780	missense	unknown
R7680:Hcn4	UTSW	9	58860671	missense	probably benign	0.08
R7915:Hcn4	UTSW	9	58823935	missense	unknown
R7956:Hcn4	UTSW	9	58844173	missense	unknown
R8146:Hcn4	UTSW	9	58823744	missense	unknown
R8234:Hcn4	UTSW	9	58844150	missense	unknown
R8421:Hcn4	UTSW	9	58858096	missense	unknown
R8690:Hcn4	UTSW	9	58843910	missense	probably benign	0.39
R8855:Hcn4	UTSW	9	58858104	missense	unknown
R8884:Hcn4	UTSW	9	58853422	missense	unknown
R9017:Hcn4	UTSW	9	58824199	missense	unknown
R9151:Hcn4	UTSW	9	58860597	missense	possibly damaging	0.94
R9331:Hcn4	UTSW	9	58860422	missense	probably damaging	0.97
R9433:Hcn4	UTSW	9	58823939	missense	unknown
R9523:Hcn4	UTSW	9	58859526	missense	unknown
R9541:Hcn4	UTSW	9	58860402	missense	probably damaging	1.00
R9730:Hcn4	UTSW	9	58824210	missense	unknown
R9748:Hcn4	UTSW	9	58823713	missense	unknown
R9753:Hcn4	UTSW	9	58844036	missense	unknown
R9795:Hcn4	UTSW	9	58853479	nonsense	probably null
RF011:Hcn4	UTSW	9	58859915	missense	unknown
X0009:Hcn4	UTSW	9	58860759	nonsense	probably null
X0057:Hcn4	UTSW	9	58859368	missense	unknown
Z1176:Hcn4	UTSW	9	58858148	missense	unknown

Predicted Primers

PCR Primer
(F):5'- TGGGAAGCTCTCAGAACACAG -3'
(R):5'- TGCGGGTCAAGGATGATTTC -3'

Sequencing Primer
(F):5'- CACAGACAAAGTGTACCCTGGTG -3'
(R):5'- CAAGGATGATTTCTGTGTTGTCCTCC -3'

Posted On

2015-04-30